Transition between cardiometabolic conditions and body weight among women: which paths increase the risk of diabetes and cardiovascular diseases?

Previous studies investigated the association of body weight and hypertension with risk of incident cardiometabolic multimorbidity. Our aim was to estimate the risk of diabetes and cardiovascular disease later in life for subjects with different progression patterns of overweight, obesity, and hypertension in mid-life. This was a prospective cohort study in which data from 12,784 participants in the Australian Longitudinal Study on Women's Health were used. Multistate model was used to study the progression pattern of overweight, obesity, hypertension, diabetes, and cardiovascular disease over the life course. The cumulative incidence of diabetes and cardiovascular disease up to the age of 73 was estimated for women with different patterns of other conditions. The six most common paths and corresponding cumulative incidences for diabetes were overweight 5.1%, obesity 11.5%, hypertension 6.9%, progression from overweight to obesity 8.2%, overweight and hypertension 12.1%, and obesity and hypertension 36.8%. For women with diabetes and other conditions, the cumulative incidence of cardiovascular disease (heart disease or stroke) as the next immediate condition was 22.4%. The corresponding figure for women who only had a report of diabetes but did not have high body weight or hypertension was 8.3%. The higher risk of transition from healthy state to a cardiometabolic condition was associated with low education, income stress, smoking, not drinking alcohol (compared to low drinkers), physical inactivity, and high perceived stress. Women with obesity and hypertension in middle-age had a substantially higher risk of developing diabetes and cardiovascular disease than women without these potentially preventable conditions.

Risk of Iron Deficiency in Women With Endometriosis: A Population-Based Prospective Cohort Study.

BACKGROUND: Endometriosis may be linked to the risk of iron deficiency through chronic systemic inflammation or heavy menstrual bleeding. No longitudinal studies, however, have examined the relationship between endometriosis and the risk of iron deficiency. METHODS: This study included 3,294 participants born from 1973 to 1978 and followed as part of the Australian Longitudinal Study on Women's Health from 2000 to 2018. Participants with endometriosis were identified using self-reported longitudinal surveys linked to administrative health records. During each survey, participants were also asked to report the diagnosis of iron deficiency, and we validated diagnoses using an administrative health database. Generalized estimating equations for binary responses with an autoregressive correlation matrix were used to examine the association between endometriosis and the risk of iron deficiency over the seven time points. FINDINGS: We found that women with endometriosis had a significantly higher risk of iron deficiency than those without endometriosis after adjusting for sociodemographic, lifestyle, reproductive, and nutrition factors (adjusted odds ratio [aOR] = 1.46; 95% confidence interval [CI] [1.29, 1.66]; p < .0001). Women with a surgically confirmed diagnosis and those with clinically suspected endometriosis had a higher risk of iron deficiency (aOR = 1.38; 95% CI [1.17, 1.64] and aOR = 1.53; 95% CI [1.30, 1.81]), respectively. These associations, however, were slightly attenuated (by 8%) when adjusted for the presence of heavy menstrual bleeding. CONCLUSIONS: Women with endometriosis are at a higher risk of developing iron deficiency than those without endometriosis. The findings suggest that iron deficiency should be concomitantly addressed during initial diagnosis and successive management of endometriosis.

Female reproductive histories and the risk of chronic obstructive pulmonary disease.

BACKGROUND: Female reproductive factors may influence the development of chronic obstructive pulmonary disease (COPD) through the female hormonal environment, but studies on this topic are limited. This study aimed to assess whether age at menarche, number of children, infertility, miscarriage, stillbirth and age at natural menopause were associated with the risk of COPD. METHODS: Women from three cohorts with data on reproductive factors, COPD and covariates were included. Cause specific Cox regression models were adjusted for birth year, race, educational level, body mass index and pack years of smoking, stratified by asthma, and incorporating interaction between birth year and time. Between cohort differences and within cohort correlations were taken into account. RESULTS: Overall, 2 83 070 women were included and 10 737 (3.8%) developed COPD after a median follow-up of 11 (IQR 10-12) years. Analyses revealed a U shaped association between age at menarche and COPD (≤11 vs 13: HR 1.17, 95% CI 1.11 to 1.23; ≥16 vs 13: HR 1.24, 95% CI 1.21 to 1.27). Women with three or more children (3 vs 2: HR 1.14, 95% CI 1.12 to 1.17; ≥4 vs 2: HR 1.34, 95% CI 1.28 to 1.40), multiple miscarriages (2 vs 0: HR 1.28, 95% CI 1.24 to 1.32; ≥3 vs 0: HR 1.36, 95% CI 1.30 to 1.43) or stillbirth (1 vs 0: HR 1.38, 95% CI 1.25 to 1.53; ≥2 vs 0: HR 1.67, 95% CI 1.32 to 2.10) were at a higher risk of COPD. Among postmenopausal women, earlier age at natural menopause was associated with an increased risk of COPD (<40 vs 50-51: HR 1.69, 95% CI 1.63 to 1.75; 40-44 vs 50-51: HR 1.42, 95% CI 1.38 to 1.47). CONCLUSIONS: Multiple female reproductive factors, including age at menarche, number of children, miscarriage, stillbirth, and age at natural menopause were associated with the risk of COPD.

The association between preconception cannabis use and gestational diabetes mellitus: The Preconception Period Analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. OBJECTIVES: We aimed to assess the association between preconception cannabis use and GDM incidence. METHODS: We analysed individual-level data from eight prospective cohort studies. We identified the first, or index, pregnancy (lasting ≥20 weeks of gestation with GDM status) after cannabis use. In analyses of pooled individual-level data, we used logistic regression to estimate study-type-specific odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders using random effect meta-analysis to combine study-type-specific ORs and 95% CIs. Stratified analyses assessed potential effect modification by preconception tobacco use and pre-pregnancy body mass index (BMI). RESULTS: Of 17,880 participants with an index pregnancy, 1198 (6.7%) were diagnosed with GDM. Before the index pregnancy, 12.5% of participants used cannabis in the past year. Overall, there was no association between preconception cannabis use in the past year and GDM (OR 0.97, 95% CI 0.79, 1.18). Among participants who never used tobacco, however, those who used cannabis more than weekly had a higher risk of developing GDM than those who did not use cannabis in the past year (OR 2.65, 95% CI 1.15, 6.09). This association was not present among former or current tobacco users. Results were similar across all preconception BMI groups. CONCLUSIONS: In this pooled analysis of preconception cohort studies, preconception cannabis use was associated with a higher risk of developing GDM among individuals who never used tobacco but not among individuals who formerly or currently used tobacco. Future studies with more detailed measurements are needed to investigate the influence of preconception cannabis use on pregnancy complications.

Fertility treatment pathways and births for women with and without polycystic ovary syndrome-a retrospective population linked data study.

OBJECTIVE: To study the fertility treatment pathways used by women with and without polycystic ovary syndrome (PCOS) and which pathways were more likely to result in a birth. DESIGN: This retrospective national community-based cohort study used longitudinal self-report survey data (collected 1996-2022; aged 18-49 years) from women born in 1973-1978 who are participants in the Australian Longitudinal Study on Women's Health. The study also used linked administrative data on fertility treatments (1996-2021). PATIENTS: Of the 8,463 eligible women, 1,109 accessed fertility treatment and were included. EXPOSURE: Polycystic ovary syndrome diagnosis was self-reported. MAIN OUTCOME MEASURE: use of ovulation induction (OI), intrauterine insemination, and/or in vitro fertilization (IVF) was established through linked administrative data. Births were self-reported. RESULTS: One in 10 of the eligible participants had PCOS (783/7,987, 10%) and 1 in 4 of the women who used fertility treatment had PCOS (274/1,109, 25%). Women with PCOS were 3 years younger on average at first fertility treatment (M = 31.4 years, SD = 4.18) than women without PCOS (M = 34.2 years, SD = 4.56). Seven treatment pathways were identified and use differed by PCOS status. Women with PCOS were more likely to start with OI (71%; odds ratio [OR] 4.20, 95% confidence interval [CI]: 2.91, 6.07) than women without PCOS (36%). Of the women with PCOS who started with OI, 46% required additional types of treatment. More women without PCOS ended up in IVF (72% vs. 51%). Overall, 63% (701/1,109) had an attributed birth, and in adjusted regressions births did not vary by last type of treatment (IVF: 67%, reference; intrauterine insemination: 67%, OR 0.94 95% CI: 0.56, 1.58; OI: 61%, OR 0.71, 95% CI: 0.52, 0.98), or by PCOS status (OR 1.27, 95% CI: 0.91, 1.77). By age, 74% of women under 35 years (471/639) and 49% of women 35 years or older had a birth. CONCLUSION: More women with PCOS used fertility treatment but births were equivalent to women without PCOS. Most women followed clinical recommendations. Births did not differ between pathways, so there was no disadvantage in starting with less invasive treatments (although there may be financial or emotional disadvantages).

Is being childless associated with a woman's risk of overweight and obesity? Results from a national longitudinal study.

AIM: To examine the association between motherhood status (mothers, voluntarily childless, involuntarily childless) and overweight and obesity over 22 years. METHODS: A total of 4092 women aged 18-23 years were followed from 1996 to 2018. Motherhood status was defined by women's reports on their fertility, attempts to conceive, use of in vitro fertilisation and fertility hormones, and number of biological children. Associations between motherhood status and overweight and obesity were examined using generalised estimating equations models, adjusting for socio-demographic characteristics, lifestyle factors, depressive symptoms, early life factors, and polycystic ovary syndrome (PCOS). RESULTS: At age 40-45 years, 12% of women were voluntarily childless and 5% were involuntarily childless. The prevalence of overweight and obesity increased with age and women who were voluntarily or involuntarily childless had higher prevalence of obesity than mothers in all surveys. After adjusting for covariates, compared with mothers, women who were voluntarily childless had higher odds of being overweight (odds ratio [OR], 95% confidence interval [CI]: 1.29, 1.09-1.52) and obese (OR, 95% CI: 1.65, 1.29-2.12). Involuntary childlessness was not associated with being overweight (OR, 95% CI: 1.05, 0.82-1.33), and its association with obesity was attenuated after adjusting for PCOS in the final model (OR, 95% CI: 1.40, 0.99-1.98). CONCLUSIONS: Around one in nine Australian women remained voluntarily childless by their late reproductive years. On average, they had higher odds of being overweight and obese than mothers, suggesting that overweight and obesity prevention programs should consider tailoring their advice by motherhood status.

Is there a link between infertility, miscarriage, stillbirth, and premature or early menopause? Results from pooled analyses of 9 cohort studies.

BACKGROUND: Some reproductive factors (such as age at menarche and parity) have been shown to be associated with age at natural menopause, but there has been little quantitative analysis of the association between infertility, miscarriage, stillbirth, and premature (<40 years) or early menopause (40-44 years). In addition, it has been unknown whether the association differs between Asian and non-Asian women, although the age at natural menopause is younger among Asian women. OBJECTIVE: This study aimed to investigate the association of infertility, miscarriage, and stillbirth with age at natural menopause, and whether the association differed by race (Asian and non-Asian). STUDY DESIGN: This was a pooled individual participant data analysis from 9 observational studies contributing to the InterLACE consortium. Naturally postmenopausal women with data on at least 1 of the reproductive factors (ie, infertility, miscarriage, and stillbirth), age at menopause, and confounders (ie, race, education level, age at menarche, body mass index, and smoking status) were included. A multinomial logistic regression model was used to estimate relative risk ratios and 95% confidence intervals for the association of infertility, miscarriage, and stillbirth with premature or early menopause, adjusting for confounders. Between-study difference and within-study correlation were taken into account by including study as a fixed effect and indicating study as a cluster variable. We also examined the association with number of miscarriages (0, 1, 2, ≥3) and stillbirths (0, 1, ≥2), and tested whether the strength of association differed between Asian and non-Asian women. RESULTS: A total of 303,594 postmenopausal women were included. Their median age at natural menopause was 50.0 years (interquartile range, 47.0-52.0). The percentages of women with premature and early menopause were 2.1% and 8.4%, respectively. The relative risk ratios (95% confidence intervals) of premature and early menopause were 2.72 (1.77-4.17) and 1.42 (1.15-1.74) for women with infertility; 1.31 (1.08-1.59) and 1.37 (1.14-1.65) for women with recurrent miscarriages; and 1.54 (1.52-1.56) and 1.39 (1.35-1.43) for women with recurrent stillbirths. Asian women with infertility, recurrent miscarriages (≥3), or recurrent stillbirths (≥2) had higher risk of premature and early menopause compared with non-Asian women with the same reproductive history. CONCLUSION: Histories of infertility and recurrent miscarriages and stillbirths were associated with higher risk of premature and early menopause, and the associations differed by race, with stronger associations for Asian women with such reproductive history.

Maternal circulating leptin, tumor necrosis factor-alpha, and interleukine-6 in association with gestational diabetes mellitus: a systematic review and meta-analysis.

Background: Over the last decade, an emerging role of novel cytokines in the pathogenesis of gestational diabetes mellitus (GDM) has been proposed. The present study was implemented to provide a more accurate estimate of the effect size of the association between leptin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and the risk of GDM.Methods: Online databases were looked up to January 2023 using the search string: (leptin OR TNF-α OR IL-6) AND "gestational diabetes." Observational studies investigating the association of selected cytokines and GDM risk were included. Odds ratios and their 95% confidence intervals (CIs) were extracted and random-effects models were used to estimate the pooled effect.Results: Twenty-four studies were included in the meta-analysis. A significant association was found between higher circulating leptin and the risk of GDM and the pooled estimate was 1.16 (95%CI: 1.07, 1.27). Higher circulating levels of IL-6 and TNF-α were associated with increased risk of GDM, and the pooled estimates were 1.35 (95%CI: 1.05, 1.73) and 1.28 (95%CI: 1.01, 1.62), respectively.Conclusions: The studied cytokines could be implicated in the GDM pathogenesis and used as potential biomarkers for assessing the GDM risk. Additional longitudinal studies with large sample sizes are needed for a further evaluation of these findings.

Associations of changes in physical activity and diet with incident obesity and changes in adiposity: Longitudinal findings from the UK Biobank.

We examined the association of changes in physical activity and diet with obesity development and changes in body fat percentage, body mass index, and waist circumference. 31,344 adults without obesity at baseline (age = 56.0 ± 7.5 years; female = 49.1%) from the UK Biobank were included. Physical activity was categorised based on public health guidelines as: inactive; insufficient; and sufficient. Diet category was assigned based on an established composited score that included consumption of fruits, vegetables, fish, red meat (unprocessed), and processed meat. Diet was categorised as: poor; reasonable; and good. Physical activity and diet changes were categorised based on changes in category: worsened; stable; increased (physical activity)/improved (diet). During a mean follow up of 6.8 (SD = ±2.3) years, 1354 (4.3%) participants developed obesity. Compared to stable physical activity-diet, increasing physical activity was associated with the lowest obesity odds, across diet changes (e.g., OR [95%CI]: diet worsened (0.89 [0.69, 1.15]); diet improved (0.65 [0.48, 0.89])). Increasing physical activity with improved diet was associated with the largest difference in body fat percentage (ß:-0.62 [-0.82, -0.41]), body mass index (-0.37 [-0.47, -0.28]), and waist circumference (-1.21 [-1.63, -0.79]). Excluding adults with a history of smoking, or major illness, lowered obesity odds among participants with increased physical activity by an additional 11%-21%. In those who decreased physical activity obesity was attenuated when combined with diet improvement. Improvements in physical activity or diet mutually attenuated the deleterious associations of the other behaviour's deterioration. In most analyses, increases in physical activity conferred consistent positive associations against the development of obesity, across dietary change groups.

Excess healthcare costs of psychological distress in young women: Evidence from linked national Medicare claims data.

The prevalence of mental health disorders in young adults is increasing, yet there is limited empirical evidence on its economic consequences. We contribute to the literature by estimating the healthcare costs of psychological distress using panel data of young women (aged 18-23 years with a 5-year follow-up) from the Australian Longitudinal Study on Women's Health and linked administrative data from Medicare Australia. Our empirical strategy is based on the classical two-part model of healthcare costs with individual specific fixed-effects. We complement our analysis with a test for selection on unobservables to address potential concerns of endogeneity. We find that young women with psychological distress have 15% higher annual healthcare costs (excluding hospital costs) than women with no psychological distress. A large proportion of these costs is driven by the use of antidepressants and the services of psychiatrists and psychologists. We further find that women with psychological distress have higher out-of-pocket costs on these mental health related services compared to non-mental health specific services. Additionally, we show that the effect of psychological distress on healthcare costs is highest during the first 6 months of onset, which gradually decreases afterwards. The findings justify the importance of policy initiatives towards early prevention and treatment of psychological distress, especially among young women.

What happens after menopause? (WHAM): A prospective controlled study of symptom profiles up to 12 months after pre-menopausal risk-reducing salpingo-oophorectomy.

OBJECTIVE: Understanding how symptoms cluster after premenopausal risk-reducing salpingo-oophorectomy (RRSO) can inform patient expectations but information is lacking. We aimed to identify symptom profiles after RRSO, changes over time, and the effect of hormone therapy (HT). METHOD: Participants were premenopausal women from a longitudinal controlled study (What Happens After Menopause? (WHAM)). Menopausal symptoms were prospectively measured in three groups: pre-menopausal comparisons who retained their ovaries (n = 99), RRSO HT users (n = 57) and RRSO non-HT users (n = 38). Symptoms (hot flashes, night sweats, low desire, vaginal dryness, poor sleep, anxiety/depression) were measured at baseline (pre-surgery) and at 3, 6 and 12 months using standardised questionnaires. Latent transition analysis was used to identify symptom profiles post-RRSO, and the probability of changing profiles over time. RESULTS: Three symptom profiles were identified: Most Symptoms (81-87% non-HT; 36-41% HT; 7-9% comparisons), Few Symptoms (7-13% non-HT; 36-42% HT; 77-80% comparisons), and Sexual Symptoms (0-10% non-HT; 17-27% HT; 14-15% comparisons). Most of the non-HT group reported Most Symptoms at 3 months with only a 2% chance of improvement by 12 months. The HT group were split between profiles at 3 months with a 5-13% chance of improvement by 6 months (14% chance of worsening), and a 12-32% chance of improvement by 12 months (4-25% chance of worsening). CONCLUSIONS: Symptoms cluster into distinct profiles after premenopausal RRSO. Most non-HT users are highly symptomatic with little chance of improvement by 12 months. In contrast, two-thirds of HT users have fewer symptoms and a much higher chance of improvement. These findings can inform patient decision-making and expectations.

Latent class trajectories of socioeconomic position over four time points and mortality: the Uppsala Birth Cohort Study.

BACKGROUND: The study assessed socioeconomic position (SEP) over four time points and employed a latent class analysis (LCA) to explore the associations between longitudinal SEP trajectories and late-life mortality. METHODS: We analyzed a cohort of 11 336 members born at the Uppsala University Hospital, Sweden during 1915-29 and followed up for mortality during 1980-2008. SEP was measured at birth, age 10, mid-adulthood and late adulthood. LCA was used to identify SEP trajectories, which were linked to all-cause and cause-specific mortality through Cox proportional hazard regression models. RESULTS: The age and birth cohort adjusted hazard ratio (HR) of all-cause mortality among the upwardly mobile from middle vs. stable low SEP was 28% lower in men [HR: 0.72; 95% confidence interval (95% CI): 0.65, 0.81] and 30% lower in women (HR: 0.70; 95% CI: 0.62, 0.78). The corresponding HR of cardiovascular mortality was 30% lower in men (HR: 0.70; 95% CI: 0.60, 0.82) and 31% lower in women (HR: 0.69; 95% CI: 0.58, 0.83). Upward mobility was also associated with decreased HR of mortality from respiratory diseases and injuries among men and from cancer, respiratory diseases, injuries and mental disorders among women. The upwardly mobile were similar to the stable high group in terms of their HRs of mortality from all-causes and cardiovascular, cancer and mental diseases. CONCLUSIONS: Upward mobility appeared to be protective of mortality from a wide range of causes. Interventions aiming to prevent deaths can benefit from creating optimal conditions earlier in the life course, letting disadvantaged children maximize their socioeconomic and health potentials.

Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: cohort study of UK Biobank participants.

STUDY QUESTION: What is the association between menopausal hormone therapy (MHT) and cause-specific mortality? SUMMARY ANSWER: Self-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes. WHAT IS KNOWN ALREADY: Evidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality. STUDY DESIGN, SIZE, DURATION: Cohort study (the UK Biobank), 178 379 women, recruited in 2006-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Postmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74). LIMITATIONS, REASONS FOR CAUTION: Self-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT. WIDER IMPLICATIONS OF THE FINDINGS: The current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation. STUDY FUNDING/COMPETING INTEREST(S): This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Infertility, recurrent pregnancy loss, and risk of stroke: pooled analysis of individual patient data of 618 851 women.

OBJECTIVE: To examine the associations of infertility, recurrent miscarriage, and stillbirth with the risk of first non-fatal and fatal stroke, further stratified by stroke subtypes. DESIGN: Individual participant pooled analysis of eight prospective cohort studies. SETTING: Cohort studies across seven countries (Australia, China, Japan, Netherlands, Sweden, the United Kingdom, and the United States) participating in the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium, which was established in June 2012. PARTICIPANTS: 618 851 women aged 32.0-73.0 years at baseline with data on infertility, miscarriage, or stillbirth, at least one outcome event (non-fatal or fatal stroke), and information on covariates were included; 93 119 women were excluded. Of the participants, 275 863 had data on non-fatal and fatal stroke, 54 716 only had data on non-fatal stroke, and 288 272 only had data on fatal stroke. MAIN OUTCOME AND MEASURES: Non-fatal strokes were identified through self-reported questionnaires, linked hospital data, or national patient registers. Fatal strokes were identified through death registry data. RESULTS: The median follow-up for non-fatal stroke and fatal stroke was 13.0 years (interquartile range 12.0-14.0) and 9.4 years (7.6-13.0), respectively. A first non-fatal stroke was experienced by 9265 (2.8%) women and 4003 (0.7%) experienced a fatal stroke. Hazard ratios for non-fatal or fatal stroke were stratified by hypertension and adjusted for race or ethnicity, body mass index, smoking status, education level, and study. Infertility was associated with an increased risk of non-fatal stroke (hazard ratio 1.14, 95% confidence interval 1.08 to 1.20). Recurrent miscarriage (at least three) was associated with higher risk of non-fatal and fatal stroke (1.35, 1.27 to 1.44, and 1.82, 1.58 to 2.10, respectively). Women with stillbirth were at 31% higher risk of non-fatal stroke (1.31, 1.10 to 1.57) and women with recurrent stillbirth were at 26% higher risk of fatal stroke (1.26, 1.15 to 1.39). The increased risk of stroke (non-fatal or fatal) associated with infertility or recurrent stillbirths was mainly driven by a single stroke subtype (non-fatal ischaemic stroke and fatal haemorrhagic stroke), while the increased risk of stroke (non-fatal or fatal) associated with recurrent miscarriages was driven by both subtypes. CONCLUSION: A history of recurrent miscarriages and death or loss of a baby before or during birth could be considered a female specific risk factor for stroke, with differences in risk according to stroke subtypes. These findings could contribute to improved monitoring and stroke prevention for women with such a history.

Menopausal hormone therapy and melanoma risk in the Australian longitudinal study on women's health.

New evidence on the association between use of menopausal hormone therapy and increased risk of cutaneous melanoma (CM) is emerging. In the Australian Longitudinal Study on Women's Health, we followed 18,850 postmenopausal women for a median of 13.2 years, and observed 356 incident CMs. We found an indication of an association between use of unopposed oestrogen therapy and CM risk (hazard ratio (HR) 1.26; 95% confidence interval (CI) 0.98, 1.61), and no association between use of oestrogen-progestin therapy and CM risk (HR 0.99; 95% CI 0.37, 2.67). More studies are needed to elucidate the potential impact of different types of hormone therapy on CM risk.

Pre-pregnancy lifestyle characteristics and risk of miscarriage: the Australian Longitudinal Study on Women's Health.

BACKGROUND: Previous studies of lifestyle characteristics and risk of miscarriage have mostly been retrospective and failed to account for induced abortions. We examine whether pre-pregnancy body-mass index, alcohol intake and smoking influence the risk of miscarriage after accounting for induced abortions. METHODS: We conducted a prospective cohort study of 9213 women with 26,594 pregnancies participating in the Australian Longitudinal Study on Women's Health. We examined whether body-mass index, smoking and alcohol intake prior to pregnancy was associated with miscarriage. We estimated adjusted relative risks (RR) using generalized estimating equations with an exchangeable correlation matrix. We explored the impact of accounting for induced abortion by first excluding all induced abortions, and secondly including 50% of induced abortions in the comparison group. RESULTS: Of the 26,592 pregnancies which occurred during the follow-up period, 19% ended in a miscarriage. We observed an increased risk of miscarriage according to pre-pregnancy obesity compared to normal weight (adjusted RR 1.13; 95% CI 1.05, 1.21), smoking between 10 and 19 cigarettes per day compared to not smoking (adjusted RR 1.13; 95% CI 1.02, 1.25), but not smoking 20 or more cigarettes per day (adjusted RR 1.07; 95% CI 0.94, 1.21) and risky drinking (≥2 units per day; adjusted RR 1.15; 95% CI 1.03, 1.28) compared to low risk drinking (< 2 units per day). The results for smoking (adjusted RR 1.09 for 10-19 cigarettes per day; 95% CI 0.98, 1.21) was attenuated after including 50% of induced abortions in the comparison group. CONCLUSIONS: We observed a modest increased risk of miscarriage according to obesity and risky alcohol intake prior to pregnancy. There was no evidence of a dose-response relationship with smoking, and the association between smoking and risk of miscarriage was attenuated after accounting for induced abortions.

Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy: A national retrospective cohort study of women in England.

OBJECTIVE: To examine the associations between adverse childhood experiences (ACE) and the risk of hysterectomy and bilateral oophorectomy in a national sample of women in England. DESIGN: Retrospective cohort study. SETTING: A stratified random sample of households across England. POPULATION: 2648 women aged ≥55 years in 2007 from the English Longitudinal Study of Ageing (ELSA) were included in the bilateral oophorectomy analyses and 2622 in the hysterectomy analyses. METHODS: Logistic and multinomial logistic regression analyses of the associations between categories of the ACE summary score (0, 1, 2, ≥3 ACE), eight individual ACE, and hysterectomy and bilateral oophorectomy. RESULTS: 615 women had undergone hysterectomy and 259 women bilateral oophorectomy. We found graded associations between the summary ACE score and risk of hysterectomy and bilateral oophorectomy. In the fully adjusted model, compared with women with no ACE, those with ≥3 ACE had double the odds of hysterectomy (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.30-3.11) and more than double the odds of bilateral oophorectomy (OR 2.61, 95% CI 1.54-4.42). The exclusion of women with cancer history made the associations stronger, especially in women who underwent hysterectomy at age <40 years or bilateral oophorectomy at age ≤44 years. Several individual ACE were positively associated with both outcomes. CONCLUSIONS: ACE are associated with increased risk of hysterectomy and bilateral oophorectomy. Individual-level covariates did not explain these associations. Our findings highlight the importance of a life course approach to understanding surgical menopause and add to our knowledge of the societal and public health impact of ACE. TWEETABLE ABSTRACT: Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy in a national sample of women in England.

Rheumatoid arthritis is a preventable disease: 11 ways to reduce your patients' risk.

New evidence shows that up to 40% of rheumatoid arthritis (RA) cases are attributable to exposure to potentially modifiable factors. We can now identify people at higher risk of RA (pre-RA) through their family history, risk factors, autoantibodies and symptoms. Counselling these patients to act to modify factors known to be associated with RA risk could prevent the development of RA, and evidence shows that informing individuals of their risk and of ways to reduce it leads to positive behavioural change and is not harmful. This consumer-focussed narrative review is targeted at primary care providers and physicians to describe 11 changes that can be made, based on current evidence linking potentially modifiable factors to RA risk. These evidence-based recommendations are: (i) cease smoking; (ii) reduce exposure to inhaled silica, dusts and occupational risks; (iii) maintain a healthy weight; (iv) increase leisure time physical activity; (v) maintain good dental hygiene; (vi) maximise breastfeeding if able; (vii) maximise dietary quality and avoid high-salt diets; (viii) consume high levels of omega-3 fatty acids and fish; (ix) reduce consumption of sugar-sweetened soft drinks; (x) consume moderate levels of alcohol; and (xi) remain vitamin D replete.

Changes in dietary patterns from preconception to during pregnancy and its association with socio-demographic and lifestyle factors.

OBJECTIVE: To examine dietary patterns changes from preconception to during pregnancy and their associations with socio-demographic and lifestyle factors. DESIGN: This study used data from the Australian Longitudinal Study on Women's Health (ALSWH), a population-based prospective cohort study. Women's dietary patterns were assessed using Healthy Eating Index-2015 (HEI-2015) score and the four patterns were obtained from the factor analysis (Western diets, vegetable and grains, traditional vegetable and fruit patterns). Multi-variable linear regression and repeated measures mixed-effect models were used. SETTING: A national representative survey which covers all Australian citizens and permanent residents in Australia. PARTICIPANTS: 621 women were included from the ALSWH. RESULTS: Women's scores increased on the 'HEI-2015', 'traditional vegetable' and 'fruit' patterns while the 'vegetable and grains' decreased from preconception to during pregnancy. Women with higher education were more likely to increase their HEI-2015 score and fruit consumption from preconception to during pregnancy, respectively (ß = 2·31, (95 % CI 0·02, 4·60)) and (ß = 23·78, (95 % CI 4·58, 42·97)), than those with lower educational status. Single women were more likely to increase the consumption of vegetables and grains compared to married women (ß = 76·08, (95 % CI 20·83, 131·32)). Women with higher income had a greater increase in the HEI-2015 score than those with lower income (ß = 3·02, (95 % CI 0·21, 5·83)). CONCLUSION: The findings indicate that there have been marked dietary changes from preconception to during pregnancy. Changes in healthy dietary patterns were influenced by education, marital status and income.